Aminopyridine derivatives having aurora a selective inhibitory action
The present invention relates to a compound of Formula (I): wherein: R 1 is H, —NHCOOR 1a , C 5-6 cycloalkyl, or phenyl; where the cycloalkyl and phenyl each independently may be substituted with one to three of the same or different substituents selected from R 10 ; R 1a is C 1-3 alkyl which may be substituted with one to three of the same or different substituents selected from F and Cl; R 2 is H, —COOH, —CH 2 COOH, —COOR 2a , or —CH 2 COOR 2a ; R 2a is C 1-2 alkyl, where the alkyl may be substituted with one to three of the same or different substituents selected from halogen atoms; R 3 is H, C 1-6 alkyl, where the alkyl may be substituted with one to three of the same or different substituents selected from R 11 ; R 10 is F, Cl, CF 3 , or C 1-2 alkyl; R 11 is halogen atom, hydroxy, or cyano; W is selected from: W 2a is H, halogen atom, cyano, C 1-2 alkyl, or C 3-5 cycloalkyl, or a pharmaceutically acceptable salt or ester thereof.
1. A compound of Formula (I):
wherein:
R 1 is H, —NHCOOR 1a , C 5-6 cycloalkyl, or phenyl, where the cycloalkyl and phenyl each independently may be substituted with one to three of the same or different substituents selected from R 10 );
R 1a is C 1-3 alkyl which may be substituted with one to three of the same or different substituents selected from F and Cl;
R 2 is H, —COOH, —CH 2 COOH, —COOR 2a , or —CH 2 COOR 2a ;
R 2a is C 1-2 alkyl, where the alkyl may be substituted with one to three of the same or different substituents selected from halogen atoms;
R 3 is H, C 1-6 alkyl, where the alkyl may be substituted with one to three of the same or different substituents selected from R 11 ;
R 10 is F, Cl, CF 3 , or C 1-2 alkyl;
R 11 is halogen atom, hydroxy, or cyano;
W is selected from:
W 2a is H, halogen atom, cyano, or C 3-5 cycloalkyl,
or a pharmaceutically acceptable salt thereof.
2. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein R 2 is —COOH or —CH 2 COOH.
3. The compound according to claim 2 or a pharmaceutically acceptable salt or ester thereof, wherein:
R 1 is —NHCOOR 1a , cyclohexyl, or phenyl, where the cyclohexyl and phenyl each independently may be substituted with one to three of the same or different substituents selected from R 10 ;
R 1a is methyl, ethyl, propyl, isopropyl, or t-butyl, any of which may be substituted with one to three of fluorine atoms; and
R 10 is F or Cl.
4. The compound according to claim 3 or a pharmaceutically acceptable salt thereof, wherein W 2a is H, cyano, or cyclopropyl.
5. A compound which is:
(a) methyl trans-5-[(tert-butoxycarbonyl)amino]-1-[4-methyl-6-(1H-pyrazol-5-ylamino)pyrimidin-2-yl]piperidine-3-carboxylate;
(b) trans-5-[(tert-butoxycarbonyl)amino]-1-[4-methyl-6-(1H-pyrazol-5-ylamino)pyrimidin-2-yl]piperidine-3-carboxylic acid;
(c) methyl cis-5-[(tert-butoxycarbonyl)amino]-1-[4-methyl-6-(1H-pyrazol-5-ylamino)pyrimidin-2-yl]piperidine-3-carboxylate;
(d) cis-5-[(tert-butoxycarbonyl)amino]-1-[4-methyl-6-(1H-pyrazol-5-ylamino)pyrimidin-2-yl]piperidine-3-carboxylic acid;
(e) methyl trans-1-[4-methyl-6-(1H-pyrazol-5-ylamino)pyrimidin-2-yl]-5-[({[(2S)-1,1,1-trifluoropropan-2-yl]oxy}carbonyl)amino]piperidine-3-carboxylate;
(f) trans-1-[4-methyl-6-(1H-pyrazol-5-ylamino)pyrimidin-2-yl]-5-[({[(2S)-1,1,1-trifluoropropan-2-yl]oxy}carbonyl)amino]piperidine-3-carboxylic acid;
(g) methyl cis-1-[4-methyl-6-(1H-pyrazol-5-ylamino)pyrimidin-2-yl]-5-[({[(2S)-1,1,1-trifluoropropan-2-yl]oxy}carbonyl)amino]piperidine-3-carboxylic acid;
(h) cis-1-[4-methyl-6-(1H-pyrazol-5-ylamino)pyrimidin-2-yl]-5-[({[(2S)-1,1,1-trifluoropropan-2-yl]oxy}carbonyl)amino]piperidine-3-carboxylic acid;
(i) methyl cis-1-[4-methyl-6-(1H-pyrazol-5-ylamino)pyrimidin-2-yl]-5-phenylpiperidine-3-carboxylate;
(j) cis-1-[4-methyl-6-(1H-pyrazol-5-ylamino)pyrimidin-2-yl]-5-phenylpiperidine-3-carboxylic acid;
(k) methyl cis-1-[4-methyl-6-(1H-pyrazol-5-ylamino)pyrimidin-2-yl]-5-[3-(trifluoromethyl)phenyl]piperidine-3-carboxylate;
(l) cis-1-[4-methyl-6-(1H-pyrazol-5-ylamino)pyrimidin-2-yl]-5-[3-(trifluoromethyl)phenyl]piperidine-3-carboxylic acid;
(m) methyl cis-5-cyclohexyl-1-[4-methyl-6-(1H-pyrazol-5-ylamino)pyrimidin-2-yl]piperidine-3-carboxylate;
(n) cis-5-cyclohexyl-1-[4-methyl-6-(1H-pyrazol-5-ylamino)pyrimidin-2-yl]piperidine-3-carboxylic acid;
(o) methyl cis-5-cyclohexyl-1-[4-methyl-6-(1,3-thiazol-2-ylamino)pyrimidin-2-yl]piperidine-3-carboxylate;
(p) cis-5-cyclohexyl-1-[4-methyl-6-(1,3-thiazol-2-ylamino)pyrimidin-2-yl]piperidine-3-carboxylic acid;
(q) methyl cis-1-{4-[(5-cyano-1,3-thiazol-2-yl)amino]-6-methylpyrimidin-2-yl}-5-cyclohexylpiperidine-3-carboxylate;
(r) cis-1-{4-[(5-cyano-1,3-thiazol-2-yl)amino]-6-methylpyrimidin-2-yl}-5-cyclohexylpiperidine-3-carboxylic acid;
(s) methyl cis-5-cyclohexyl-1-{4-[(5-cyclopropyl-1,3-thiazol-2-yl)amino]-6-methylpyrimidin-2-yl}piperidine-3-carboxylate;
(t) cis-5-cyclohexyl-1-{4-[(5-cyclopropyl-1,3-thiazol-2-yl)amino]-6-methylpyrimidin-2-yl}piperidine-3-carboxylic acid;
(u) methyl cis-5-cyclohexyl-1-{4-[(3-cyclopropyl-1H-pyrazol-5-yl)amino]-6-methylpyrimidin-2-yl}piperidine-3-carboxylate;
(v) cis-5-cyclohexyl-1-{4-[(3-cyclopropyl-1H-pyrazol-5-yl)amino]-6-methylpyrimidin-2-yl}piperidine-3-carboxylic acid;
(w) methyl (cis-5-cyclohexyl-1-{4-[(3-cyclopropyl-1H-pyrazol-5-yl)amino]-6-methylpyrimidin-2-yl}piperidin-3-yl)acetate;
(x) (cis-5-cyclohexyl-1-{4-[(3-cyclopropyl-1H-pyrazol-5-yl)amino]-6-methylpyrimidin-2-yl}piperidin-3-yl)acetic acid;
(y) methyl {cis-5-cyclohexyl-1-[4-methyl-6-(1,3-thiazol-2-ylamino)pyrimidin-2-yl]piperidin-3-yl}acetate, or
(z) {cis-5-cyclohexyl-1-[4-methyl-6-(1,3-thiazol-2-ylamino)pyrimidin-2-yl]piperidin-3-yl}acetic acid,
or a pharmaceutically acceptable salt thereof.
6. A pharmaceutical composition comprising, together with pharmaceutically acceptable carrier or diluent, at least one compound according to claim 1 as active ingredient.